Method and apparatus for indetification of counterfeit drugs, pharmaceuticals, or medicines

ABSTRACT

Systems and methods for measuring the isotope ratio of one or more gaseous oxides produced during combustion of drugs, pharmaceuticals, or medicines aiming to detect counterfeit drugs, pharmaceuticals, or medicines based on comparison of the isotopic composition of the tested drugs, pharmaceuticals, or medicines with the isotopic composition of the authentic products.

CROSS-REFERENCES TO RELATED APPLICATIIONS

This application claims the benefit of, and priority to, U.S.provisional Patent application No. 62/535,505 filed Jul. 21, 2017, thecontents of which are hereby incorporated by reference.

BACKGROUND OF THE INVENTION

A counterfeit drug (or pharmaceutical, medicine) is a medication orpharmaceutical product which is produced and sold with the intent todeceptively represent its origin, authenticity or effectiveness. TheWorld Health Organization defines a counterfeit drug as anypharmaceutical product that is deliberately mislabeled with respect toidentity and/or source. Counterfeit drugs may include branded andgeneric products, may contain no active ingredient, the wrong activeingredient or the wrong amount of the correct active ingredient.

The U.S. Food and Drug Administration warns that “an individual whoreceives a counterfeit drug may be at risk of a number of dangeroushealth consequences. Patients may experience unexpected side effects,allergic reactions, or a worsening of their medical condition. TheCenters for Disease Control and Prevention estimates that 10%-30% ofmedicines sold in developing countries are counterfeit.

Detecting counterfeit products is one of the ways to combat thisproblem. Different analytical techniques such as Fourier transforminfrared spectroscopy, NIR spectroscopy, X-ray powder diffraction,thermal gravimetric analysis, microscopy, and various forms ofchromatography have been used to check for frauds. Other techniques usedfor chemical fingerprinting to identify counterfeits include gaschromatography, ion chromatography, capillary electrophoresis, andelemental analysis. However, most of them are rather expensive andresource intensive.

BRIEF SUMMARY OF INVENTION

Embodiments of the present invention relate to systems and methods fordetection of counterfeit drugs based on comparison of the isotopiccomposition of the tested drugs, pharmaceuticals, or medicines with theisotopic composition of the authentic products.

In one aspect of the present invention is a transformation of the testeddrugs, pharmaceuticals, or medicines partially or completely intogaseous oxides by combustion reactions. A combustion reaction is thechemical term for a process known more commonly as burning. Combustionreaction is a type of chemical reaction involving two substances whichusually include oxygen and heat. This approach provides a universalsolution, because the absolute majority of drugs, pharmaceuticals, ormedicines consist of at least one of the following elements, such ascarbon, nitrogen, hydrogen, and sulfur, which produce gaseous oxidesduring the combustion process.

An embodiment in accordance with the present invention further comprisesmeasurements of the isotopic compositions of the produced oxides byisotopic ratio gas analyzers based on one of the optical absorptionspectroscopy methods.

The present invention provides systems and methods for determiningcounterfeit drugs, pharmaceuticals, or medicines.

BRIEF DESCRIPTION OF THE SEVERAL VIEWS OF THE DRAWING

FIG. 1. A method of determining counterfeit drugs, pharmaceuticals, ormedicines, the method comprising of the steps of: converting the drugs,pharmaceuticals, or medicines into gaseous oxides by combustion withoxygen in a combustion chamber; delivering the produced gaseous oxidesto an optical absorption spectroscopy based isotopic ratio gas analyzerand diluting them by a balance gas; measuring isotopic composition ofgaseous oxides; providing data about composition of the gaseous oxidesproduced by combustion.

DETAILED DESCRIPTION OF THE INVENTION

One of the most precise methods of identifying counterfeit drugspharmaceuticals, or medicines includes analysis of the chemicalcomposition of the tested drug material and its encapsulation material.While this method can be extremely precise, it usually requiresexpensive equipment and complex analysis. An alternative approach is tocombust (burn) a drug, a pharmaceutical, or a medicine completely inzero air or in pure oxygen, which implies converting the drug,pharmaceutical, or medicine into gas phase oxides and measuring theamount of different gaseous oxides produced during the combustionreaction and the isotopic composition of the produced gaseous oxides.Isotope composition analysis of the following oxides can be routinelyperformed by an optical absorption based gas analyzer: CO—CarbonMonoxide, CO₂—Carbon Dioxide, N₂O—Nitrogen Dioxide, NO—Nitric Oxide,NO₂—Nitrogen Dioxide, H₂O—Water, H₂O₂—Hydrogen Peroxide, SO₂—SulfurDioxide, SO₃—Sulfur Trioxide, and CIO—Chlorine Monoxide.

These gaseous oxides are important for analysis because carbon,nitrogen, sulfur, and hydrogen are the main atomic components of themajority of drugs, pharmaceuticals, or medicines. If liquid samples haveto be tested, they can be dried out first, and then solutes can beconverted to oxides by the combustion process. Solvents can also beseparated from solutes and can be converted to oxides for furtherisotopic composition analysis of solvents. The obtained isotopiccompositions can be checked with the reference isotopic compositionssupplied by the drug manufacture. The obtained isotopic compositions canalso be sent to a drug manufacture for confirmation of the origin ofdrugs, pharmaceuticals, or medicines, or sent to a third party forverification.

Embodiments of the present invention provide systems and methods fordetermining counterfeit drugs, pharmaceuticals, or medicines based onthe transformation of the tested drugs, pharmaceuticals, or medicinesinto gaseous oxides. The isotopic compositions of these oxides can beprecisely performed by optical absorption spectroscopy methods.

According to an embodiment, isotopic composition of gaseous oxidesproduced from drug, pharmaceutical, or medicine compounds can bemeasured by the Tuned Diode Laser Absorption Spectroscopy (TDLAS)method. Modern TDLAS based instruments provide isotopic compositionmeasurement precisions better than 0.5% for δ13 C in CO₂ (CampbellScientific, Inc. TGA200A Trace Gas Analyzer) and better than 0.15% forδ13 C in CO₂ (Thermo Scientific Delta Ray Isotope Ratio InfraredSpectrometer)

According to another embodiment, isotopic composition of gaseous oxidesproduced from drug, pharmaceutical, or medicine compounds can bemeasured by the Cavity Enhanced Absorption Spectroscopy (CEAS) method.

According to yet another embodiment, isotopic composition of gaseousoxides produced from drug, pharmaceutical, or medicine compounds can bemeasured by the Cavity Ring-Down Spectroscopy (CRDS) method. Modern CRDSbased instruments provide isotopic composition measurement precisionsbetter than 0.1% for δ13 C in CO₂ (Picarro G2131-i Analyzer), 0.1% forδD in H₂O (Picarro L2140-i Analyzer), and 0.5% for δ15N in N₂O (PicarroG5131-i Analyzer).

According to an embodiment, isotopic composition of gaseous oxidesproduced from drug, pharmaceutical, or medicine compounds can bemeasured by the Integrated Cavity Output Spectroscopy (ICOS) method.Modern ICOS based instruments provide isotopic composition measurementprecisions better than 0.1% for δ13 C in CO₂, (LGR-ABB: Carbon DioxideIsotope Analyzer—Elevated CO₂), 0.2% for δD in H₂O (LGR-ABB: LiquidWater Isotope Analyzer).

According to an embodiment, drugs, pharmaceuticals, or medicines can betransformed to gaseous oxides by combustion reactions. Combustion of thetested samples will produce oxides with isotopic composition reflectingthe isotopic composition of the tested samples.

According to yet another embodiment, drugs, pharmaceuticals, ormedicines in liquid form can be dried before they are conveted togaseous oxides.

According to an embodiment, the isotopic compositions of measured oxidesare compared with the isotopic compositions oxides produced from controlsamples.

In one aspect of the present invention, the amount of produced gaseousoxides can also be measured. These measurements provide additional andvery important data about the chemical composition of the testedsamples.

According to an embodiment, gaseous oxides produced during thecombustion process are diluted by a balance gas. Examples of balancegases are: nitrogen, oxygen, helium, neon, argon, zero air. The dilutionstep may be required if concentrations of the produced oxides are toohigh for the optimal operation of an optical absorption spectroscopybased isotopic ratio analyzer. It is important that the dilution stepdoesn't change isotopic compositions of gaseous oxides.

FIG. 1 shows a schematic of a system for drugs, pharmaceuticals, ormedicines authenticity verification, the system comprising: a combustionchamber for converting the tested drugs, pharmaceuticals, or medicinesinto gaseous oxides, a source of oxygen, and an optical absorptionspectroscopy based isotopic ratio gas analyzer to measure said gaseousoxides produced in the combustion chamber, wherein the system is capableto dilute gaseous oxides formed through the combustion process by abalance gas

Taking into account that the combustion process can be easilystandardized and the modern isotopic ratio analyzers are quite preciseand accurate, the proposed method may become a very powerful tool todistinguish counterfeit drugs, pharmaceuticals, and medicines fromauthentic products.

All references, including publications, patent applications, andpatents, cited herein are hereby incorporated by reference to the sameextent as if each reference were individually and specifically indicatedto be incorporated by reference and were set forth in its entiretyherein.

The use of the terms “a” and “an” and “the” and “at least one” andsimilar referents in the context of describing the disclosed subjectmatter (especially in the context of the following claims) are to beconstrued to cover both the singular and the plural, unless otherwiseindicated herein or clearly contradicted by context. The use of the term“at least one” followed by a list of one or more items (for example, “atleast one of A and B”) is to be construed to mean one item selected fromthe listed items (A or B) or any combination of two or more of thelisted items (A and B), unless otherwise indicated herein or clearlycontradicted by context. The terms “comprising,” “having,” “including,”and “containing” are to be construed as open-ended terms (i.e., meaning“including, but not limited to,”) unless otherwise noted. Recitation ofranges of values herein are merely intended to serve as a shorthandmethod of referring individually to each separate value falling withinthe range, unless otherwise indicated herein, and each separate value isincorporated into the specification as if it were individually recitedherein. All methods described herein can be performed in any suitableorder unless otherwise indicated herein or otherwise clearlycontradicted by context. The use of any and all examples, or examplelanguage (e.g., “such as”) provided herein, is intended merely to betterilluminate the disclosed subject matter and does not pose a limitationon the scope of the invention unless otherwise claimed. No language inthe specification should be construed as indicating any non-claimedelement as essential to the practice of the invention.

Certain embodiments are described herein. Variations of thoseembodiments may become apparent to those of ordinary skill in the artupon reading the foregoing description. The inventors expect skilledartisans to employ such variations as appropriate, and the inventorsintend for the embodiments to be practiced otherwise than asspecifically described herein.

Accordingly, this disclosure includes all modifications and equivalentsof the subject matter recited in the claims appended hereto as permittedby applicable law. Moreover, any combination of the above-describedelements in all possible variations thereof is encompassed by thedisclosure unless otherwise indicated herein or otherwise clearlycontradicted by context.

1) A system for a product authenticity verification, the systemcomprising: a combustion chamber for converting the said product intogaseous oxides, a source of oxygen with known isotopic composition, andan optical absorption spectroscopy based isotope ratio gas analyzer tomeasure an isotopic composition of a gaseous oxide produced in thecombustion chamber, and capable of measuring the isotopic composition atleast one of the following gaseous oxides: CO, CO₂, N₂O, NO, NO₂, H₂O,H₂O₂, SO₂, SO₃, CIO, wherein the product comprises at least one of adrug, a pharmaceutical, a vaccine, or a medicine. 2) The system of claim1, wherein the isotope ratio analyzer is in fluid communication with thecombustion chamber. 3) The system of claim 1 further comprises a meanscapable of delivering the product to the combustion chamber. 4) Thesystem of claim 1 further comprises a means capable of measuring anamount of the gaseous oxide formed through the combustion. 5) The systemof claim 1, wherein source of oxygen with known isotopic composition isa zero air made from the ambient air. 6) The system of claim 1, whereinthe system is capable to dilute the gaseous oxide formed through thecombustion process by a balance gas. 7) The system of claim 1 furthercomprises a means capable of separating a solvent from the product in aform of a liquid solution. 8) The system of claim 1, wherein the isotoperatio analyzer is a Tuned Diode Laser Absorption Spectroscopy based gasanalyzer. 9) The system of claim 13, wherein the isotope ratio analyzeris a Cavity Ring-Down Spectroscopy based gas analyzer. 10) The system ofclaim 1, wherein the isotope ratio analyzer is an Integrated CavityOutput Spectroscopy based gas analyzer. 11) The system of claim 1,wherein the isotope ratio analyzer is a Photo-Acoustic Spectroscopybased gas analyzer. 12) The system of claim 1, wherein the isotope ratioanalyzer is a Non Dispersive Infrared Spectroscopy based gas analyzer.13) The system of claim 1, wherein the isotope ratio analyzer is aFourier-Transform Spectroscopy based gas analyzer. 14) The system ofclaim 1, wherein the isotope ratio analyzer is a Frequency CombSpectroscopy based gas analyzer.